title: A link between premenopausal iron deficiency and breast cancer malignancy.
abstract: BACKGROUND
  Young breast cancer (BC) patients less than 45 years old are at higher risk of dying from the disease when compared to their older counterparts. However, specific risk factors leading to this poorer outcome have not been identified.
  
  
  METHODS
  One candidate is iron deficiency, as this is common in young women and a clinical feature of young age. In the present study, we used immuno-competent and immuno-deficient mouse xenograft models as well as hemoglobin as a marker of iron status in young BC patients to demonstrate whether host iron deficiency plays a pro-metastatic role.
  
  
  RESULTS
  We showed that mice fed an iron-deficient diet had significantly higher tumor volumes and lung metastasis compared to those fed normal iron diets. Iron deficiency mainly altered Notch but not TGF-β and Wnt signaling in the primary tumor, leading to the activation of epithelial mesenchymal transition (EMT). This was revealed by increased expression of Snai1 and decreased expression of E-cadherin. Importantly, correcting iron deficiency by iron therapy reduced primary tumor volume, lung metastasis, and reversed EMT markers in mice. Furthermore, we found that mild iron deficiency was significantly associated with lymph node invasion in young BC patients (p<0.002).
  
  
  CONCLUSIONS
  Together, our finding indicates that host iron deficiency could be a contributor of poor prognosis in young BC patients.
authors.affiliation: Department of Environmental Medicine, New York University (NYU), New York, NY 10016, USA.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Jian
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Shao
authors.forename: Deborah
authors.initials: D
authors.lastname: Axelrod
authors.forename: Julia
authors.initials: J
authors.lastname: Smith
authors.forename: Baljit
authors.initials: B
authors.lastname: Singh
authors.forename: Stephanie
authors.initials: S
authors.lastname: Krauter
authors.forename: Luis
authors.initials: L
authors.lastname: Chiriboga
authors.forename: Zhaoxu
authors.initials: Z
authors.lastname: Yang
authors.forename: Jinqing
authors.initials: J
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000150:complications* / Q000473:pathology*; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D000090463:Iron Deficiencies; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D017697:Premenopause / Q000378:metabolism*; D014183:Transplantation, Heterologous